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Biomedical subjects

I Azuma

Publications and source records attributed to I Azuma.

At least 271 records · Page 15Linked to original sources

Adjuvant activities of quinonyl-N-acetyl muramyl dipeptides in mice and guinea pigs.

The adjuvant and tumor-suppressive activities of the quinonyl [2,3-dimethoxy-5-methyl-6-(9'-carboxynonyl)-1,4-benzoquinone (QS-10)] derivatives of N-acetyl muramyl dipeptides were examined. N-Acetyl muramyl-L-valyl-D-isoglutamine (MurNac-L-Val-D-isoGln), QS-10-MurNAc-L-Val-D-isoGln, and their methyl esters were shown to have potent adjuvant activity on the induction of delayed-type hypersensitivity to monoazobenzenarsonate-N-acetyl-L-tyrosine in guinea pigs and on the primary immune response against sheep erythrocytes in vitro; however, only QS-10-MurNAc-L-Val-D-isoGln methyl ester, i.e., QS-10-MurNAc-L-Val-D-Glu(OCH3)NH2 (quinonyl-MDP-66), was shown to be an active adjuvant for the induction of allogeneic killer T cells in mice and the suppression of tumor growth in syngeneic mice when it was administered as a suspension in phosphate-buffered saline. The effectiveness of the chain length of the quinonyl moiety in quinonyl-MDP-66 and the replacement of the L-valine residue with L-serine or L-threonine were also examined in comparison with the adjuvant and tumor-suppressive activities of quinonyl-MDP-66.

Acetylmuramyl-Alanyl-Isoglutamine↗

Stimulation of nonspecific resistance to infection induced by 6-O-acyl muramyl dipeptide analogs in mice.

The experimental system utilized in investigating the correlation between the chemical structures of muramyl peptides and their protective activities in the sepsis type of systemic infections caused by Escherichia coli was applied in evaluating the enhancement of resistance to infection induced by 32 synthetic glycopeptide analogs, including 6-O-acyl derivatives and 1-alpha-O-benzyl derivatives of muramyl dipeptide (N-acetyl muramyl-L-alanyl-D-isoglutamine). In assessing the 6-O-acyl derivatives of muramyl dipeptide, we found that the degree of protective activity was attributable to the kinds of fatty acids introduced. Acylation of the 6-hydroxy group on the muramic acid moiety in muramyl dipeptide with natural mycolic acid or a synthetic fatty acid possessing either an alpha-branched or an alpha-branched, beta-hydroxylated group resulted in a decrease in or a disappearance of the protective activity of muramyl dipeptide. Acylation with a normal fatty acid or an iso fatty acid resulted in a retention or enhancement of muramyl dipeptide activity. The activity of acylated derivatives containing linear fatty acids was stimulated by increasing the chain length up to 18 carbon atoms. The highest degree of protective activity occurred with the derivatives acylated with straight-chain fatty acids, particularly with the derivatives acylated with palmitic acid and arachidic acid. Benzylation of the 1-hydroxy group of muramyl dipeptide resulted in a decrease in or a loss of protective activity.

Acetylmuramyl-Alanyl-Isoglutamine↗

Adjuvant activity of 6-amino-6-deoxy-muramyldipeptides and their acylamino derivatives on the induction of delayed hypersensitivity to azobenzenearsonate-N-acetyl-L-tyrosine in guinea pigs.

The 6-amino-6-deoxy-N-acetylmuramyldipeptides and their 6-acylamino derivatives were shown to be active as adjuvants on the induction of delayed-type hypersensitivity to azobenzenearsonate-N-acetyl-l-tyrosine in guinea pigs. However, 6-acylamino-6-deoxy-N-(acyl)muramyldipeptides were inactive as adjuvants.

Acetylmuramyl-Alanyl-Isoglutamine↗

Adjuvant activity of carbohydrate analogs of N-acetylmuramyl-L-alanyl-D-isoglutamine on the induction of delayed-type hypersensitivity to azobenzenearsonate-N-acetyl-L-tyrosine in guinea pigs.

The adjuvant activity of 29 kinds of carbohydrate analogs of N-acetylmuramyl-L-alanyl-D-isoglutamine on the induction of delayed-type hypersensitivity to azobenzenearsonate-N-acetyl-L-tyrosine was examined in guinea pigs. It was found that the D-manno- and D-galacto-type muramyldipeptides were as active as the D-gluco-type muramyldipeptide (MDP). The structural requirement of the carbohydrate moiety of analogs of N-acetylmuramyl-L-alanyl-D-isoglutamine is discussed.

Acetylmuramyl-Alanyl-Isoglutamine↗

Persistence of protein, carbohydrate and was components of tubercle bacilli in dermal BCG lesions.

Dermal tuberculous lesions were produced in rabbits with Bacille Calmette Guèrin and biopsied on days 4, 14, 21, 35, and 56. Frozen sections prepared from the biopsy specimens were stained by the peroxidase-antiperoxidase immunocytochemical technique with antisera against whole tubercle bacilli and antisera against the protein B, polysaccharide I, and wax D fractions of tubercle bacilli. In the primary lesions, protein B was often undetectable at 21 days, and polysaccharide I was often undetectable at 35 days. Wax D disappeared more slowly than the other bacillary components evaluated, and some wax D was still found at 56 days (if the lesions had not completely healed). Antisera against intact tubercle bacilli produced results similar to those produced by antiserum against wax D. These studies suggest that the chronicity of tuberculous lesions is due, at least in part, to the persistence of the wax D-like component of tubercle bacilli.

Animals↗

Suppression of BCG cell wall induced delayed-type hypersensitivity by BCG pre-treatment. I. Induction of adherent suppressor cells by live BCG injection and their characterization.

Previous injections of live Bacillus Calmette-Guérin (BCG) in mice produced a suppression of delayed-type hypersensitivity (DTH) induced by oil-treated BCG cell walls (CW). This phenomenon was analysed by the macrophage migration inhibition (MI) test in which peritoneal exudate cells (PEC) from live BCG-injected mice were mixed with PEC from BCG CW-immunized mice, with the result that the former cells suppressed the MI activity in the latter. We considered the Mi test to be a reliable method for demonstrating the existence of suppressor cells induced by the injection of live BCG. Moreover, we found that the adherent cells of PEC possessed a suppressive effect which was retained even after treatment with either anti-mouse Ig or anti-brain associated theta (BA theta) antigen; that the PEC from mice injected with live BCG on at least the 12th day before cell harvesting showed the suppression; and that the suppression operated across the H-2 barrier.

Animals↗

Inhibition of pulmonary granuloma formation in mice by treatment with Mycobacterial protoplasm and immuno-suppressants and its relation to protection against aerosol infection with virulent Mycobacterium tuberculosis.

Because the pulmonary granuloma formation by mycobacterial cell walls (CW) is likely mediated by cellular immunity, the effect of specific antigens and various immunosuppressants on pulmonary granuloma formation and protection against virulent m. tuberculosis, strain H37Rv was investigated in mice immunized with oil-treated CW from BCG or M. Tuberculosis, strain Aoyama B. Results of desensitization experiments with specific antigens showed that multiple intravenous injections of BCG protoplasm inhibited the footpad delayed hypersensitivity, macrophage migration inhibitory activity of lung cells and pulmonary granuloma formation as well as the enhancement of resistance against aerosol challenge with M, tuberculosis, strain H37Rv. However, treatment with nonspecific immunosuppressants like con A, silica or carrageenan induced only abrogation of footpad delayed hypersensitivity but not prevention of pulmonary granuloma formation or resistance against aerosol challenge. These results suggest a close relationship between pulmonary granuloma formation and protection against H37Rv in mice immunized with oil-treated mycobacterial CW.

Aerosols↗

Adjuvant and mitogenic activities of niacine derivatives and their NAD-analogs.

The effects of niacine derivatives and their corresponding NAD-analogs on the immune response in vivo and in vitro and the mitogenic activity were investigated. The compounds III, IIIa, IV, V and Va act as adjuvants on the production of circulating antibody to bacterial alpha-amylase in guinea pigs when they were immunized as water-in-oil emulsion. All the compounds at 10-micrograms dose can act as adjuvant on the primary immune response to sheep erythrocytes in vitro. However it was shown that all the compounds had slight or no adjuvant activity on the induction of delayed-type hypersensitivity to ABA-N-acetyl-L-tyrosine. The compounds I, Ia and II were mitogenic in normal mouse spleen cells.

Acetylmuramyl-Alanyl-Isoglutamine↗

Enhancement by immunostimulants of the production by mouse spleen cells of factor(s) stimulating differentiation of mouse myeloid leukemic cells.

Mouse myeloid leukemic Ml cells can be induced to differentiate into macrophages and granulocytes in vitro by a factor(s) stimulating differentiation of the cells (D-factor) or by various chemical compounds. Spleen lymphocytes and spleen macrophages have been shown to produce D-factor when treated with various mitogens including lipopolysaccharide or synthetic double-stranded polyribonucleotide, poly(I) . poly(C). Several immunostimulants from microorganisms were tested for ability to induce differentiation of Ml cells and to stimulate production of D-factor by spleen cells. Mycobacterium bovis BCG (500 micrograms/ml) and the cell wall skeleton of Nocardia rubra (50 micrograms/ml) induced differentiation of Ml cells; but Corynebacterium parvum CN6134 and the cell wall skeleton of Propionibacterium acnes C7 had no effect on Ml cells. On the other hand, all immunostimulants tested at concentrations of more than 10 micrograms/ml were found to stimulate production of D-factor by both spleen lymphocytes and spleen macrophages. Synthetic derivatives of N-acetylmuramyl dipeptide(MDP), the minimal adjuvant-active subunit of the bacterial cell wall, had no direct effect on the differentiation of Ml cells and only slightly stimulated the production of D-factor by spleen cells. Therefore, the structure of microorganisms required for induction of differentiation of Ml cells and for stimulation of production of D-factor are suggested to be different from that of MDP.

Acetylmuramyl-Alanyl-Isoglutamine↗

Combined treatment of syngeneic murine tumors and xenotransplanted human lung cancer by immunotherapy and radiotherapy.

The synergistic effect of nonspecific immunotherapy with cell-wall skeleton of BCG on radiotherapy against two syngeneic murine tumors, a methylcholanthrene-induced tumor (MCA) and a spontaneous well-differentiated mammary adenocarcinoma (Br-1), was studied in (+/+) balb/c mice and (nu/nu) mice of BALB/c background. Single irradiation of tumors with a dose of 2000 rad induced complete shrinkage in about 18% of MCA and Br-1 tumors in (+/+) mice. Single irradiation did not induce complete shrinkage of tumors in (nu/nu) mice. When immunotherapy was combined with radiotherapy, the rates of complete shrinkage of MCA and Br-1 tumors increased to 82 and 61%, respectively. In contrast, such a strong synergistic effect was not observed in (nu/nu) mice. Moreover, human lung cancers (two squamous cell carcinomas and two small cell carcinomas) xenotransplanted to nude mice were treated with the combined therapy. The effect was stronger on squamous cell carcinomas than on small cell carcinomas.

Animals↗

Killing of tumor cells in vitro by macrophages from mice given injections of squalene-treated cell wall skeleton of Nocardia rubra.

Peritoneal exudate cells (PEC) harvested from mice after i.p. injection of squalene-treated cell wall skeleton of Nocardia rubra (N. rubra-CWS) demonstrated vigorous cytolytic activity in vitro toward tumor target cells. Fractionation of these PEC by adherence to plastic dishes showed that the cytolytic activity in PEC was associated with an adherent phagocytic cell. Induction of the cytolytic adherent PEC required an optimal dose of 50 micrograms N. rubra-CWS and i.p. injection. Cytolytic activity of N. rubra-CWS-induced adherent PEC was maximal after 5 days and fell steadily thereafter. Susceptible tumor targets included cells syngeneic, allogeneic, and xenogeneic to the effector cell source. In contrast, nonneoplastic xenogeneic cells were not affected by N. rubra-CWS-induced adherent PEC. The effector cells were not found in the spleen or peripheral lymph nodes. In addition, the cytolytic activity of N. rubra-CWS-induced adherent PEC was completely inhibited by treatment with antimacrophage serum and complement or carrageenan. Treatment with monoclonal anti-Thy 1.2 antibody and complement, however, did not affect the cytolytic activity of the adherent PEC. These features make it likely that N. rubra-CWS-induced cytolytic effector cells are macrophages.

Animals↗

Antimetastatic effect of cell-wall skeleton of Propionibacterium acnes C7 on Lewis lung carcinoma in C57BL/6J mice.

The effect of the cell-wall skeleton (CWS) of Propionibacterium acnes C7 on the metastasis of Lewis lung carcinoma in C57BL/6J mice was examined. Intratumoral or intravenous injection of P. acnes-CWS was effective for both prolongation of the survival period and protection against pulmonary metastases, but intraperitoneal injection was ineffective in tumor-bearing mice. Intratumoral injection of P. acnes-CWS also inhibited lymph node metastases and produced some complete tumor regressions. These cured mice were rechallenged with the same tumor but no evidence of transplantation resistance was found. On the other hand, neither inhibition of lymph node metastases nor complete tumor regressions were observed in the groups treated with intravenous and intraperitoneal injection of P. acnes-CWS. Intrapleural injection of P. acnes-CWS after surgical excision of the primary tumor was also effective for the prolongation of survival period but not for protection against pulmonary metastases.

Adjuvants, Immunologic↗

Differentiation and production of colony-stimulating factor induced by immunostimulants in a leukemia cell line.

Immunostimulants from various microorganisms were tested on a myeloid leukemia cell line (M1) for the ability to induce production of CSF and to cause differentiation of these cells. Based on their activities, the compounds were divided into two general classes: those inducing extensive cellular differentiation and those devoid of this effect. The stimulants which were active in this regard always produced large quantities of CSF, whereas those devoid of a differentiating effect did not cause CSF production. Even the potent stimulants had no effect on the D subline, in which the differentiation was not inducible.

Adjuvants, Immunologic↗